This study examined the clinical course and outcome of COVID-19 infection in hemodialysis patients in PMC. It included all patients infected with COVID from PMC kidney dialysis unit. Data was collected for 103 patients undergoing hemodialysis with laboratory-confirmed COVID-19 diagnosis from the beginning of the pandemic until the end date for data collection, between January 2020 - April 2022.
The findings of this study showed that COVID-19 adversely impacted hemodialysis patients, the study population was divided into 3 groups, a group that died after COVID-19 accounting for 31% of the patients, a group that survived after the infection but their frequency of dialysis has increased (36.4%), and the third group (33.6%) was already at the maximum number of weekly dialysis before COVID-19, and remained on the same number of dialysis post COVID-19 infection, this group was excluded from the statistical analysis, as it could not be ruled out whether the number of dialysis remained the same as it was at its maximum per the hospital protocol, or because there was no need for the increase.
In our study 32 patient died after their infection with COVID-19 with a percentage of 31%, a study in HD units in Madrid, Spain reported that dialysis constituted the highest risk of death for COVID-19 patient during the first month of diagnosis, similarly in our study the patients died immediately after they got the infection [9]. Other studies also found that the morbidity and mortality following COVID-19 infection was a lot higher in hemodialysis patients than in the general population [10–13].
Symptoms of COVID-19 in this study sample included acute pain in different body parts in addition to cough in all patients, other symptoms occured at varying percentages such as SOB, chest pain, headache, arthritis, dermatitis, fever and diarrhea (Fig. 1). Even though these are the general symptoms that also exist in non-dialysis patients, hemodialysis patients have worse symptoms of COVID-19 because they tend to be elderly and to have multiple comorbid conditions, like hypertension, DM, coronary artery disease, CKD, heart failure and suppressed immune systems [14]. In our study, the recorded symptoms were mild to moderate and drugs have been used to alleviate these symptoms including antibiotics like azithromycin, clindamycin, ceftazidime, cefuroxime, etc., as well as pain management, antipyretic and anti-inflammatory medications including paracetamol, aspirin, hydrocortisone, and various vitamins and mineral supplements (Data not shown).
For the patients included in statistical analysis, the A blood group was the most common and they were significantly affected with an increase in the frequency of dialysis after having the COVID − 19 infection. Previous studies that were performed in many countries such as China and Canada have shown a significant association between blood group A and the complications after COVID-19 infection [15]. Another comprehensive review also found that the A blood type was associated with more COVID infection susceptibility while the O blood type was more protective [16].
The proposed mechanism behind this is that the patients with group A blood type higher levels of ACE 1 and ACE 2, which increases the affinity of SARS-COV-2 to theses receptors resulting in more severe infection, while the O group produces anti-A antibodies that bind with A-like antigen, which is created from SARS-COV-2 virus envelope, resulting in prevention of infection [15]. Another suggested mechanism is the inhibition of the virus adhesion to the host cell via two ways either by anti-A antibody binding to the SARS-COV-2 S protein, and blocking the interaction between this protein and ACE 2 receptors to prevent the virus from lung entry, or via SARS-COV-2 glycan antigen, which is similar to antigen A but does not exist in the O blood group, so it is proposed that the patients with the A blood group have a greater risk of COVID-19 severity as they lack anti-A antibodies [15].
While the previously mentioned studies found that patients with group O had the least severity and mortality, in our study the O blood group was associated with a higher percentage of fatality (Table 2). A recently published study on the effect of COVID-19 on recovered patients in Palestine found no association between the blood groups and post COVID outcomes [17]. The issue of blood group and severity of COVID-19 complications has not been resolved yet with different studies showing controversial results [15].
Approximately, more than half of the infected patients were males (60%), this is probably because males in Palestine tend to be more socially active than females, and according to many previous studies that had been done in many different countries, it was reported that women were more responsible in dealing with the COVID-19 pandemic than men, who had an irresponsible attitude that manifested by their lower rate of hand washing and wearing of face masks [18]. Also, it was shown that males had a higher risk of death, as two thirds of dead patients were males [18], but in our study this difference was not statistically significant (p = 0.687) (Table 2).
As for the age, there was no statistically significant difference between the age groups (p = 0.236). Many comorbidities were recorded with a significant association with dialysis frequency changes, this outcome can be justified by the age of the patients included in the study as most of them were elderly and suffered from chronic diseases, and according to a nationwide analysis in China, COVID-19 patients with underlying comorbidities had more severe COVID-19 infection and poorer clinical outcomes compared to patients without comorbidities [19].
The most common comorbidity recorded in our study was DM, which significantly affected the outcome on hemodialysis patients increasing the frequency of dialysis or mortality (p-value = 0.031), DM is a risk factor for kidney failure as high levels of sugar in the blood damage the filtering units in kidney and that can lead to a significant damage including end stage kidney failure that requires dialysis [8].
In August 2020, WHO announced that there was an association between cardiovascular disease and COVID-19, as there was an increased risk of both arterial and venous thrombotic complications and after 7 days of COVID-19 diagnosis the risk of MI was doubled [20]. A study in the city of Mus in Turkey recommended that patients who are on dialysis must take prophylactic anticoagulant and antiplatelet agents while they are infected with COVID-19 [21]. Despite the risk of bleeding, the risk of thrombosis is still considered higher compared to the general population. According to our study, there is a significant association between acute MI and COVID-19 outcomes in dialysis patients, and it was associated with a higher mortality rate. Most of the patients in our study were on aspirin or other anticoagulant therapy like enoxaparin, this is important as hemodialysis patients require special attention to prevent the risk of thromboembolic events including MI [21, 22].
Another cardiovascular comorbidity that has a significant correlation with dialysis and COVID-19 outcomes is pre-existing hypertension. The findings of many observational studies in China demonstrated that the majority of the COVID-19 patients with hypertension were at a higher risk of developing severe outcomes of dialysis deterioration, one of them, is the increase in dialysis frequency [23]. All of the hypertensive patients in our study had a significant increase in the number of dialysis sessions after COVID-19 infection. There are two suggested explanations for this either via the renin angiotensin system or by causing endothelial dysfunction by producing high amount of pro-inflammatory agents such as angiotensin II, cytokines, interleukin-6 and tumor necrosis factor-α causing an imbalance between relaxing and constrictor factors, moreover, hypertension is one of main contributing factors to kidney dysfunction, if the blood pressure is not controlled, it can lead to AKI in dialysis patients [23, 24]. However, more studies are required to confirm the association between hypertension and increased risk of complications in dialysis patients who are affected by COVID-19.
AKI was defined, based on KDIGO classification, as a change in either SCr, by 0.3mg/dL over two days or an increase in SCr 1.5 times more than the baseline within the last 7 days, or urine output less than 0.5mL/kg/hr. for 6 hours. In addition, being elderly with hypertension and DM are considered as risk factors for AKI. COVID-19 targets ACE receptors which can be associated with adverse clinical outcomes in COVID patients including AKI [25]. In our study there was no significant relation between AKI and frequency of dialysis (p = 0.463), this could be due to the small sample size, nevertheless many studies indicate a significant association between kidney abnormalities and COVID-19 complications [25–27].
Our study included six patients who had a kidney transplant, and after COVID-19 infection 3 of them died and 3 continued to live with kidney failure, according to a multi-center study done in France, a high mortality rate was reported among the recipients of kidney transplant who got coronavirus infection [28].
Both SCr and BUN are indicators for kidney function. In the healthy patient, SCr normal level is between 0.59 to 1.35 mg/dL and BUN is between 6–24 mg/dL. According to our study, more than half of the patients who had a high BUN and raised level of SCr had an increase in the number of their dialysis frequency which indicate there is an association between them (Table 2).
Our results show that lower serum calcium in patients with COVID-19 increased dialysis frequency (Table 2), while the mechanism behind this is still unknown in detail, a few studies have demonstrated that SARS-COV specific gene (E) encodes a small transmememium protein that translate onto a permeable calcium channel, resulting in more calcium entery from inside the cells [29].
In our study, there were five patients with hypokalemia, three of them died after COVID-19 infection, the number of patients is too small and the association was not statistically significant (p = 0.498), another study found that hypokalemia was common among COVID-19 patients and it was accompanied with hypocalcemia [30].